N J Taylor1, G K Manakkat Vijay, R D Abeles, G Auzinger, W Bernal, Y Ma, J A Wendon, D L Shawcross. 1. Liver Intensive Care Unit, King's College London School of Medicine at King's College Hospital, London, UK; Institute of Liver Studies and Transplantation, King's College London School of Medicine at King's College Hospital, London, UK.
Abstract
BACKGROUND: Patients with cirrhosis are susceptible to sepsis, pre-disposing to the development of encephalopathy, bleeding and organ dysfunction with associated high mortality. AIM: To characterise circulating neutrophil function in a cirrhotic cohort as a determinant of 90-day and 1-year mortality. METHODS: Sixty-two patients with cirrhosis [49 stable (Child-Pugh A/B/C = 24%/39%/37%); 13 acute-on-chronic liver failure] were prospectively studied and compared with 11 healthy controls. Neutrophil function was evaluated at baseline and repeated at critical points during the course of the patient's illness until death/transplantation. Neutrophil phenotype was determined using fluorochrome-labelled antibodies to CD16/CD11b and assessed by flow cytometry. Neutrophil phagocytic activity (NPA) and capacity (NPC) were determined using FITC-labelled opsonised Escherichia coli. Oxidative burst (OB) was quantified by the percentage of neutrophils producing reactive oxygen species (ROS) and mean fluorescence intensity at rest, and after stimulation with E. coli. Physiological variables, biochemistry, microbiology and outcomes were collected. Plasma pro- and anti-inflammatory cytokine profiles were performed by ELISA. RESULTS: NPA/NPC was impaired in cirrhosis with the most significant dysfunction being observed in those with advanced disease and in those treated with propranolol. NPC predicted survival in stable cirrhosis [AUROC 0.83 (95% CI 0.68-0.97); P = 0.021] and differentiated survivors from nonsurvivors (90-day P = 0.01; 1 year P < 0.001). Resting OB ≥12% predicted 90-day mortality with 80% sensitivity and 71% specificity [AUROC 0.81 (95% CI 0.64-0.97); P = 0.026 and differentiated survivors from nonsurvivors; P = 0.015]. CONCLUSION: Circulating neutrophils in patients with cirrhosis are dysfunctional and predict the development of infection, organ dysfunction and survival at 90 days and 1 year.
BACKGROUND:Patients with cirrhosis are susceptible to sepsis, pre-disposing to the development of encephalopathy, bleeding and organ dysfunction with associated high mortality. AIM: To characterise circulating neutrophil function in a cirrhotic cohort as a determinant of 90-day and 1-year mortality. METHODS: Sixty-two patients with cirrhosis [49 stable (Child-Pugh A/B/C = 24%/39%/37%); 13 acute-on-chronic liver failure] were prospectively studied and compared with 11 healthy controls. Neutrophil function was evaluated at baseline and repeated at critical points during the course of the patient's illness until death/transplantation. Neutrophil phenotype was determined using fluorochrome-labelled antibodies to CD16/CD11b and assessed by flow cytometry. Neutrophil phagocytic activity (NPA) and capacity (NPC) were determined using FITC-labelled opsonised Escherichia coli. Oxidative burst (OB) was quantified by the percentage of neutrophils producing reactive oxygen species (ROS) and mean fluorescence intensity at rest, and after stimulation with E. coli. Physiological variables, biochemistry, microbiology and outcomes were collected. Plasma pro- and anti-inflammatory cytokine profiles were performed by ELISA. RESULTS: NPA/NPC was impaired in cirrhosis with the most significant dysfunction being observed in those with advanced disease and in those treated with propranolol. NPC predicted survival in stable cirrhosis [AUROC 0.83 (95% CI 0.68-0.97); P = 0.021] and differentiated survivors from nonsurvivors (90-day P = 0.01; 1 year P < 0.001). Resting OB ≥12% predicted 90-day mortality with 80% sensitivity and 71% specificity [AUROC 0.81 (95% CI 0.64-0.97); P = 0.026 and differentiated survivors from nonsurvivors; P = 0.015]. CONCLUSION: Circulating neutrophils in patients with cirrhosis are dysfunctional and predict the development of infection, organ dysfunction and survival at 90 days and 1 year.
Authors: Thomas H Tranah; Godhev K Manakkat Vijay; Jennifer M Ryan; R Daniel Abeles; Paul K Middleton; Debbie L Shawcross Journal: Am J Physiol Gastrointest Liver Physiol Date: 2017-06-22 Impact factor: 4.052
Authors: Cornelius Engelmann; Christina Becker; Andreas Boldt; Toni Herta; Albrecht Boehlig; Katrin Splith; Moritz Schmelzle; Niklas Mueller; Sandra Krohn; Hans-Michael Tautenhahn; Michael Bartels; Ulrich Sack; Thomas Berg Journal: Sci Rep Date: 2016-12-05 Impact factor: 4.379
Authors: A Horvath; B Leber; B Schmerboeck; M Tawdrous; G Zettel; A Hartl; T Madl; S Stryeck; D Fuchs; S Lemesch; P Douschan; E Krones; W Spindelboeck; F Durchschein; F Rainer; G Zollner; R E Stauber; P Fickert; P Stiegler; V Stadlbauer Journal: Aliment Pharmacol Ther Date: 2016-09-04 Impact factor: 8.171